Crystallization is one of the most widely used separation processes in the chemical and pharmaceutical industries, with some 80% of products going through a crystallisation step at some point in their manufacture.
Crystallisation determines product quality, such as desired morphology and size distribution for subsequent filtering, washing, reaction with other chemicals, transporting, tableting, packaging and storage.
However, despite its importance and significant research efforts, crystallisation remains one of the least well understood and most difficult manufacturing processes to control. For example, at present there is no way to monitor and control primary nucleation.
Primary nucleation can be homogeneous or heterogeneous.
Homogeneous primary nucleation is the initial formation of crystal nuclei where there are no other crystals present at all. Heterogeneous primary nucleation is where impurities that are present induce the formation of crystals either spontaneously or due to a change in environmental conditions (such as a drop in temperature, for example). This is distinct from secondary nucleation where the formation of crystal nuclei is attributable to the presence of existing microscopic crystals, which have been deliberately added, i.e., seeding.
Generally, primary nucleation cannot be monitored or controlled because the size of the nuclei generated is too small and the concentration of the nuclei generated is too low to detect using currently available techniques. Therefore, at present there is no way to separate and independently study the nucleation of crystal nuclei and the growth of crystals. The ability to carry out such studies would be of significant importance as nucleation largely dictates the final characteristics of a crystal.
EP1965900 describes a crystallisation apparatus having independent temperature control in different process zones. However, there is no clear way to separate and/or control nucleation and growth of crystals. Also, it is known to induce nucleation using ultrasound, but such devices are generally very expensive, energy intensive and in some cases unreliable. Using seed crystals (“seeding”) is the most common method of inducing nucleation in industrial crystallisation operations, primarily because it can provide the final crystals with the same characteristics as the seed crystals. However, seeding requires a large number of experimental tests to be carried out in order to understand the effect of size, amount and quality of the seeds on the properties of the crystallised product so obtained.
Therefore, it is an object of the invention to overcome at least some of the disadvantages of the prior art.
Further aims and objects of the invention will be apparent from the description herein and the advantages provided by the invention.